Ubiquitination Pathway

Ubiquitination, also known as ubiquitylation, regulates degradation of cellular proteins by the ubiquitinproteasome system, controlling a protein’s half-life and expression levels. This process involves the sequential action of ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). The reaction catalyzed by each enzyme transfers a covalent bond with ubiquitin from one enzyme to the next and finally to a target protein. Formation of polyubiquitin chains occurs when the target protein is another ubiquitin molecule already covalently linked to another protein. Mammalian genomes encode approximately 12 E1 enzymes, 30–40 E2 enzymes, and hundreds of E3 enzymes. The diversity of these enzymes also suggests a wide variety of protein targets or functions with different regulatory mechanisms for each one. For example, monoubiquitination of cell surface transmembrane receptors marks them for endocytosis, and polyubiquitin chains act as scaffolds for ubiquitin-binding proteins. The degradation of proteins via the ubiquitin-proteasome system regulates their cellular lifetime. In addition, this system processes foreign proteins in antigen-presenting cells to facilitate immune responses. Disruption of the ubiquitin-proteasomal degradation pathway has been implicated in a wide range of human diseases, such as cancer, diabetes, and cardiovascular and neurodegenerative diseases. ...

Read more

Ubiquitination, also known as ubiquitylation, regulates degradation of cellular proteins by the ubiquitinproteasome system, controlling a protein’s half-life and expression levels. This process involves the sequential action of ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). The reaction catalyzed by each enzyme transfers a covalent bond with ubiquitin from one enzyme to the next and finally to a target protein. Formation of polyubiquitin chains occurs when the target protein is another ubiquitin molecule already covalently linked to another protein. Mammalian genomes encode approximately 12 E1 enzymes, 30–40 E2 enzymes, and hundreds of E3 enzymes. The diversity of these enzymes also suggests a wide variety of protein targets or functions with different regulatory mechanisms for each one. For example, monoubiquitination of cell surface transmembrane receptors marks them for endocytosis, and polyubiquitin chains act as scaffolds for ubiquitin-binding proteins. The degradation of proteins via the ubiquitin-proteasome system regulates their cellular lifetime. In addition, this system processes foreign proteins in antigen-presenting cells to facilitate immune responses. Disruption of the ubiquitin-proteasomal degradation pathway has been implicated in a wide range of human diseases, such as cancer, diabetes, and cardiovascular and neurodegenerative diseases.